Update on estimated PML risk related to fingolimod

An updated estimate on the global risk of progressive multifocal leukoencephalopathy (PML) in 299,600 MS patients receiving fingolimod showed that the PML risk associated with fingolimod is low, estimated at 0.13 per 1,000 patients over a 5-year period[1]. The risk appears to increase with cumulative exposure. PML risk could be increased if fingolimod treatment is started at a relatively high age.

Potential PML cases from the manufacturer's safety database (data cut-off 28 February 2020) were reviewed by an independent PML adjudication committee. The number of confirmed PML cases was compared with the estimated global number of fingolimod-treated patients and patient-years of exposure. Approximately 299,600 patients were treated with fingolimod globally, covering >778,900 patient-years (PYs) of exposure.

The number of suspected PML cases reported and evaluated was 188. Of these:

• 37 cases were associated with fingolimod treatment;
• 17 cases were attributed to previous natalizumab treatment; and
• 134 cases were not confirmed as PML based on reported information.

Based on these numbers, the estimated crude incidence was 0.12 (95% CI 0.09-0.17) per 1,000 patients. The estimated incidence rate was 4.75 (95% CI 3.34-6.55) per 100,000 PYs. The incidence of PML appeared to increase with treatment duration, approaching a plateau in year 5 at ~0.13 per 1,000 patients, with a wide confidence interval.

The exact pattern of the relationship to duration of treatment remains unclear. PML incidence appeared to increase between 30 and 50 years of age and then stabilise or even decrease, but the exact shape of the relationship with age is also uncertain. For both treatment duration and age at treatment initiation, the incidence estimates lacked precision due to the small number of cases.

1. Fox R, et al. Update on the risk estimates of progressive multifocal leukoencephalopathy related to fingolimod. MSVirtual 2020, Abstract FC02.02.

 



Posted on 25 November 2020